Dynamic interplay between histone H3 modifications and protein interpreters: emerging evidence for a "histone language"

Histone proteins organize DNA into dynamic chromatin structures and regulate processes such as transcription, repair, and replication. Control of chromatin function and structure is mediated in part by reversible post-translational modifications (PTMs) on histones. The most N-terminal region of histone H3 contains a high density of modifiable residues. Here we focus on the dynamic interplay between histone modification states on the H3 N terminus and the binding modules that recognize these states. Specifically, we discuss the effect of auxiliary modifications to H3K4unmod/me3 binding modules (specifically H3R2 methylation, H3T3 phosphorylation, and H3T6 phosphorylation). Emerging evidence suggests that histone PTMs behave less like a strict "code", but more like a "language", which better illustrates the importance of context. Using androgen-receptor-mediated gene activation as an example, we propose a model of how the combinatorial natures of PTMs on the H3 N terminus and the complexes that recognize these epigenetic modifications control gene expression.